Send to

Choose Destination
Pharmacol Biochem Behav. 2005 Dec;82(4):695-703. Epub 2006 Jan 4.

Probable activation of the opioid receptor-nitric oxide-cyclic GMP-K+ channels pathway by codeine.

Author information

Laboratorio de Farmacología Area Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo ExHacienda la Concepción Carr, Mexico.


There is evidence that local peripheral administration of morphine produces antinociception through the activation of the nitric oxide (NO)-cyclic GMP-K(+) channels pathway. Therefore we evaluated the possible participation of this pathway in the antinociceptive action produced by codeine in the rat 5% formalin test. Local peripheral injection of codeine produced a dose-dependent antinociception during the first and second phases of the test. Local pretreatment of the paws with the NO synthase inhibitor N(G)-L-nitro-arginine methyl ester (L-NAME), the soluble guanylyl cyclase inhibitor methylene blue, the ATP-sensitive K(+) channel inhibitors glibenclamide and tolbutamide, the non-selective voltage-gated K(+) channel inhibitors 4-aminopyridine (4-AP) and tetraethylammonium (TEA) and the opioid receptor blocker naloxone prevented codeine-induced antinociception in both phases of the test. L-NAME, methylene blue, K(+) channel blockers and naloxone by themselves did not modify formalin-induced nociceptive behavior. Our data suggest that codeine could activate the opioid receptor-NO-cyclic GMP-K(+) channels pathway in order to produce its peripheral antinociceptive effect in the formalin test.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center